The purpose of this study was to clarify the endogenous system to protect the psychiatric disease. Firstly, DNA array showed more than 100 molecules expressed highly in the mouse brain by environmental enrichment for 4 weeks. One of them, dynorphin A, an endogenous opioid peptide, increased by the running wheel in the brain. Additionally, dynorphin A (1-13), a potent fragment of this peptide prevented repeated stress-induced behavioral impairments in mice. These results suggest that dynorphin might be induced to express in the brain by enriched environment and might alleviate the stress-induced behavioral impairments.